This proposal seeks NIH funding to support the seventh in a series of scientific meetings on systems biology approaches to understanding gene regulation in eukaryotes. The proposed 2010 meeting will focus on five key aspects of gene regulation-cis-regulatory logic, transcriptional regulatory networks, nucleosomes and epigenetics, post-transcriptional regulation, and variation and evolution of regulatory networks. In addition, a session will be devoted to emerging technologies for analysis of gene regulation. The 2012 and 2014 meetings will follow a similar format and will include topics highly relevant to the current research at the time of the meeting. How cells control gene expression is a fundamental problem in biology. Ever since the discovery of the genes and the double strand helix structure of the DNA, there have been continuous investigations into this problem. Many great discoveries have been made, including the nuclear machineries that make transcripts as well as the DNA sequences that serve to control gene expression. Despite these efforts, our knowledge of the molecular mechanisms of gene regulation remains sketchy. For example, the transcriptional regulatory sequences and the regulatory proteins for most genes in the human genome are still poorly defined, despite the availability of the complete genome sequences. Now, with the amount of genome sequence information for various organisms rapidly growing, the problem has become ever more pressing. Traditionally, investigators have studied gene regulation by analyzing the DNA-binding preferences of specific transcription factors and/or the cis-regulatory elements that control the expression patterns of single genes. These studies have tentatively identified DNA sequence motifs for around one hundred transcription factors, and have led to the idea that transcriptional regulation at the genome level involves a complex interplay between modular DNA sequence elements such as enhancers, silencers, insulators, and basal promoter elements. The last several years have seen rapid advances in the development of new genomics approaches to analysis of each step of the gene expression. Many of these approaches involve a computational component in their design or interpretation. Other strategies have evolved from the availability of several complete genomic sequences and the prospects of many more to come. These include analyses of sequence conservation among closely related species to detect "phylogenetic footprints" in non-coding regions and the use of genomic microarrays and next-generation sequencing technologies to study DNA-protein and RNA-protein interactions. The results from these new approaches have provided unprecedented details on the gene regulatory processes in prokaryotic as well as eukaryotic cells. It is clear that effective collaborations between experimental and computational biologists will be required to come to grips with the complex problem of gene regulation. Thus we propose to conduct a meeting to permit a free cross-disciplinary exchange of existing ideas and expertise. It is hoped that this meeting will provide a mechanism for the establishment of new collaborations, and a forum for discussing new experimental and computational approaches. The meeting will be held at Cold Spring Harbor Laboratory on March 23-27, 2010. Twenty-two speakers of international renown have been invited to give oral presentations, and approximately forty-five others will be selected from submitted abstracts from applicants to the meeting. With the exception of the keynote address, oral presentations will be 15'in length with 5'for questions and discussions. Poster sessions will be included to encourage meaningful participation by the non-speaking attendees. In addition, we will hold pre-meeting workshops which will familiarize molecular biologists and bioinformaticians with the key concepts, terminology and acronyms needed to understand each others'disciplines. We expect attendance of approximately 250-300 scientists at the meeting. We particularly encourage female scientists and junior investigators to participate - one of the two keynote speakers, 25% of the remaining invited speakers, and two of the four meeting organizers are women, and the majority of the participants in previous years have been students, postdocs or investigators in their early independent career. PUBLIC HEALTH RELEVANCE: Ever since the discovery of genes and the double strand helix structure of the DNA, a central question has concerned how these genes are switched on and off in the cell. Decades of research have contributed to a robust understanding of the basic mechanisms of gene expression, and in recent years efforts have turned towards how sets of genes are turned on or off together. With the outpouring of enormous amounts of biological information about the relation between gene expression and genome architecture (DNA sequence, DNA structure and modification, chromatin structure and modification etc.), a variety of different scientific disciplines have become necessary. Biologists and computer scientists are using these approaches to shed light on the principles underlying the orchestration of sets of genes in normal cellular states and how global regulation can become derailed in disease states such as cancer. This biennial international conference (2010, 2012 and 2014) will provide a forum for these scientists to share their latest discoveries and will bring together the leading experts in the field.